A Study of Atezolizumab (an Engineered Anti-Programmed Death-Ligand 1 [PD-L1] Antibody) as Monotherapy or in Combination With Bevacizumab (Avastin®) Compared to Sunitinib (Sutent®) in Participants With Untreated Advanced Renal Cell Carcinoma

NCT ID: NCT01984242

Last Updated: 2019-12-23

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

305 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-01-08

Study Completion Date

2019-01-08

Brief Summary

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This multicenter, randomized, open-label study will evaluate the efficacy, safety and tolerability of atezolizumab as monotherapy or in combination with bevacizumab versus sunitinib in participants with histologically confirmed, inoperable, locally advanced or metastatic renal cell carcinoma who have not received prior systemic therapy either in the adjuvant or metastatic setting.

Detailed Description

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Conditions

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Renal Cell Carcinoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Atezolizumab and Bevacizumab

Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) will be administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.

Group Type EXPERIMENTAL

Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody

Intervention Type DRUG

Atezolizumab will be administered according to the dosage schedule mentioned in the arm description.

Bevacizumab

Intervention Type DRUG

Bevacizumab will be administered according to the dosage schedule mentioned in the arm description.

Atezolizumab

Atezolizumab 1200 mg will be administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except European Union \[EU\] participants) can crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.

Group Type EXPERIMENTAL

Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody

Intervention Type DRUG

Atezolizumab will be administered according to the dosage schedule mentioned in the arm description.

Bevacizumab

Intervention Type DRUG

Bevacizumab will be administered according to the dosage schedule mentioned in the arm description.

Sunitinib

Sunitinib 50 mg will be administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants can crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.

Group Type ACTIVE_COMPARATOR

Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody

Intervention Type DRUG

Atezolizumab will be administered according to the dosage schedule mentioned in the arm description.

Bevacizumab

Intervention Type DRUG

Bevacizumab will be administered according to the dosage schedule mentioned in the arm description.

Sunitinib

Intervention Type DRUG

Sunitinib will be administered according to the dosage schedule mentioned in the arm description.

Interventions

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Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody

Atezolizumab will be administered according to the dosage schedule mentioned in the arm description.

Intervention Type DRUG

Bevacizumab

Bevacizumab will be administered according to the dosage schedule mentioned in the arm description.

Intervention Type DRUG

Sunitinib

Sunitinib will be administered according to the dosage schedule mentioned in the arm description.

Intervention Type DRUG

Other Intervention Names

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Tecentriq MPDL3280A RO5541267 Avastin Sutent

Eligibility Criteria

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Inclusion Criteria

* Unresectable advanced or metastatic renal cell carcinoma with component of clear cell histology and/or component of sarcomatoid histology that has not been previously treated with any systemic agents, including treatment in the adjuvant setting
* Measurable disease, as defined by RECIST v1.1
* Karnofsky performance score greater than or equal to (\>/=) 70
* Adequate hematologic and end-organ function as defined by protocol
* Women of childbearing potential and male participants with partners of childbearing potential must agree to use highly effective methods of contraception as defined by protocol

Exclusion Criteria

Disease-Specific Exclusions:

* Radiotherapy for renal cell carcinoma within 14 days prior to Cycle 1, Day 1 with the exception of single-fraction radiotherapy given for the indication of pain control
* Known active malignancies or metastasis of the brain or spinal cord or leptomeningeal disease, as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments
* Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
* Uncontrolled hypercalcemia or symptomatic hypercalcemia
* Malignancies other than renal cell carcinoma within 5 years prior to Cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death, treated with expected curative outcome

General Medical Exclusions:

* Life expectancy of less than (\<) 12 weeks
* Pregnant and lactating women
* History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
* History of autoimmune disease
* History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
* Participants with active or chronic hepatitis B, active hepatitis C, Human Immunodeficiency Virus (HIV) positive test, significant cardiovascular disease
* Prior allogeneic stem cell or solid organ transplant


* Prior treatment with Cluster of Differentiation 137 (CD137) agonists, anti-Cytotoxic T-Lymphocyte Antigen-4 (anti-CTLA-4), anti-programmed death-1 (anti-PD-1), or anti-PD-L1 therapeutic antibody or pathway-targeting agents
* Treatment with systemic immunostimulatory agents for any reason within 6 weeks or five half-lives of the drug, whichever is shorter, prior to Cycle 1, Day 1
* Treatment with systemic immunosuppressive medications within 2 weeks prior to Cycle 1, Day 1

Bevacizumab- and Sunitinib-Specific Exclusions:

* Inadequately controlled hypertension
* Prior history of hypertensive crisis or hypertensive encephalopathy
* New York Heart Association Class II or greater congestive heart failure
* History of myocardial infarction or unstable angina, stroke or transient ischemic attack within 3 months prior to Cycle 1, Day 1
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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HonorHealth Research Institute - Bisgrove

Scottsdale, Arizona, United States

Site Status

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Site Status

UCLA

Los Angeles, California, United States

Site Status

University of California

San Francisco, California, United States

Site Status

Univ Colorado Health Sci Ctr

Aurora, Colorado, United States

Site Status

Rocky Mountain Cancer Ctr - Denver (Williams)

Denver, Colorado, United States

Site Status

Yale Uni School of Medicine; Section of Medical Oncology

New Haven, Connecticut, United States

Site Status

Georgetown U; Lombardi Comp Can

Washington D.C., District of Columbia, United States

Site Status

SCRI Florida Cancer Specialists South

Fort Myers, Florida, United States

Site Status

Mayo Clinic-Jacksonville

Jacksonville, Florida, United States

Site Status

Florida Cancer Specialist, North Region

St. Petersburg, Florida, United States

Site Status

The University of Chicago

Chicago, Illinois, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Dana Farber Cancer Inst.

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

Karmanos Cancer Institute.

Detroit, Michigan, United States

Site Status

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

Site Status

Memorial Sloan-Kettering

New York, New York, United States

Site Status

Oncology Hematology Care Inc

Cincinnati, Ohio, United States

Site Status

Cleveland Clinic Foundation; Taussig Cancer Center

Cleveland, Ohio, United States

Site Status

Oncology Associates of Oregon, P.C

Eugene, Oregon, United States

Site Status

Northwest Cancer Specialists, P.C.

Tigard, Oregon, United States

Site Status

Tennessee Oncology PLLC - Nashville (20th Ave)

Nashville, Tennessee, United States

Site Status

Vanderbilt Medical Center

Nashville, Tennessee, United States

Site Status

Texas Oncology-Baylor Sammons Cancer Center

Dallas, Texas, United States

Site Status

Fakultni nemocnice Olomouc

Olomouc, , Czechia

Site Status

Hopital Europeen Georges Pompidou; Service D'Oncologie Medicale

Paris, , France

Site Status

CHU Bordeaux

Pessac, , France

Site Status

Institut Gustave Roussy; Departement Oncologie Medicale

Villejuif, , France

Site Status

Medizinische Hochschule; Zentrum Innere Medizin; Abt. Hämatologie u. Onkologie

Hanover, , Germany

Site Status

Klinikum d.Universität München Campus Großhadern

München, , Germany

Site Status

Klinikum rechts der Isar der TU München; Klinikapotheke

München, , Germany

Site Status

Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 2

Milan, Lombardy, Italy

Site Status

Medical Oncology, Arezzo

Arezzo, Tuscany, Italy

Site Status

Azienda Ospedaliera Universitaria Senese, U.O.C. Immunoterapia Oncologica

Siena, Tuscany, Italy

Site Status

Centrum Med. Ostrobramska NZOZ Magodent

Warsaw, , Poland

Site Status

Prof. Dr. I. Chiricuta Institute of Oncology

Cluj-Napoca, , Romania

Site Status

Medisprof SRL

Cluj-Napoca, , Romania

Site Status

Clinica Universitaria de Navarra

Pamplona, Navarre, Spain

Site Status

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Site Status

Hospital Clinic de Barcelona. Unidad de Nuevas Terapias;Oncology Department

Barcelona, , Spain

Site Status

Hosp de Madrid Norte Sanchinarro; Centro Integral; Onco Clara Campal

Madrid, , Spain

Site Status

Barts and the London NHS Trust.

London, , United Kingdom

Site Status

Royal Marsden Hospital - London

London, , United Kingdom

Site Status

Christie Hospital Nhs Trust; Medical Oncology

Manchester, , United Kingdom

Site Status

Countries

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Ukraine United States Czechia France Germany Italy Poland Romania Spain United Kingdom

References

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Aldin A, Besiroglu B, Adams A, Monsef I, Piechotta V, Tomlinson E, Hornbach C, Dressen N, Goldkuhle M, Maisch P, Dahm P, Heidenreich A, Skoetz N. First-line therapy for adults with advanced renal cell carcinoma: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2023 May 4;5(5):CD013798. doi: 10.1002/14651858.CD013798.pub2.

Reference Type DERIVED
PMID: 37146227 (View on PubMed)

Pal SK, McDermott DF, Atkins MB, Escudier B, Rini BI, Motzer RJ, Fong L, Joseph RW, Oudard S, Ravaud A, Bracarda S, Suarez C, Lam ET, Choueiri TK, Ding B, Quach C, Hashimoto K, Schiff C, Piault-Louis E, Powles T. Patient-reported outcomes in a phase 2 study comparing atezolizumab alone or with bevacizumab vs sunitinib in previously untreated metastatic renal cell carcinoma. BJU Int. 2020 Jul;126(1):73-82. doi: 10.1111/bju.15058. Epub 2020 Apr 24.

Reference Type DERIVED
PMID: 32233107 (View on PubMed)

Other Identifiers

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2013-003167-58

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

WO29074

Identifier Type: -

Identifier Source: org_study_id